Donna B. Stolz

Bio: Donna B. Stolz is an academic researcher from University of Pittsburgh. The author has contributed to research in topics: Hepatocyte & Transplantation. The author has an hindex of 96, co-authored 399 publications receiving 30926 citations. Previous affiliations of Donna B. Stolz include University of California, San Francisco.

Stem Cell Characteristics of Amniotic Epithelial Cells

Abstract: Amniotic epithelial cells develop from the epiblast by 8 days after fertilization and before gastrulation, opening the possibility that they might maintain the plasticity of pregastrulation embryo cells. Here we show that amniotic epithelial cells isolated from human term placenta express surface markers normally present on embryonic stem and germ cells. In addition, amniotic epithelial cells express the pluripotent stem cell-specific transcription factors octamer-binding protein 4 (Oct-4) and nanog. Under certain culture conditions, amniotic epithelial cells form spheroid structures that retain stem cell characteristics. Amniotic epithelial cells do not require other cell-derived feeder layers to maintain Oct-4 expression, do not express telomerase, and are nontumorigenic upon transplantation. Based on immunohistochemical and genetic analysis, amniotic epithelial cells have the potential to differentiate to all three germ layers--endoderm (liver, pancreas), mesoderm (cardiomyocyte), and ectoderm (neural cells) in vitro. Amnion derived from term placenta after live birth may be a useful and noncontroversial source of stem cells for cell transplantation and regenerative medicine.

Carbon nanotubes degraded by neutrophil myeloperoxidase induce less pulmonary inflammation

Abstract: We have shown previously that single-walled carbon nanotubes can be catalytically biodegraded over several weeks by the plant-derived enzyme, horseradish peroxidase1. However, whether peroxidase intermediates generated inside human cells or biofluids are involved in the biodegradation of carbon nanotubes has not been explored. Here, we show that hypochlorite and reactive radical intermediates of the human neutrophil enzyme myeloperoxidase catalyse the biodegradation of single-walled carbon nanotubes in vitro, in neutrophils and to a lesser degree in macrophages. Molecular modelling suggests that interactions of basic amino acids of the enzyme with the carboxyls on the carbon nanotubes position the nanotubes near the catalytic site. Importantly, the biodegraded nanotubes do not generate an inflammatory response when aspirated into the lungs of mice. Our findings suggest that the extent to which carbon nanotubes are biodegraded may be a major determinant of the scale and severity of the associated inflammatory responses in exposed individuals.

Linking of Autophagy to Ubiquitin-Proteasome System Is Important for the Regulation of Endoplasmic Reticulum Stress and Cell Viability

Abstract: Two major protein degradation systems exist in cells, the ubiquitin proteasome system and the autophagy machinery. Here, we investigated the functional relationship of the two systems and the underlying mechanisms. Proteasome inhibition activated autophagy, suggesting that the two are functionally coupled. Autophagy played a compensatory role as suppression of autophagy promoted the accumulation of polyubiquitinated protein aggregates. Autophagy was likely activated in response to endoplasmic reticulum stress caused by misfolded proteins during proteasome inhibition. Suppression of a major unfolded protein response pathway mediated by IRE1 by either gene deletion or RNA interference dramatically suppressed the activation of autophagy by proteasome inhibitors. Interestingly, c-Jun NH 2 -terminal kinase (JNK) but not XBP-1, both of which are the known downstream targets of IRE1, seemed to participate in autophagy induction by proteasome inhibitors. Finally, proteasome inhibitor-induced autophagy was important for controlling endoplasmic reticulum stress and reducing cell death in cancer cells. Our studies thus provide a mechanistic view and elucidate the functional significance of the link between the two protein degradation systems.

Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells

Abstract: Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).

Extracellular vesicles: exosomes, microvesicles, and friends.

Abstract: Cells release into the extracellular environment diverse types of membrane vesicles of endosomal and plasma membrane origin called exosomes and microvesicles, respectively. These extracellular vesicles (EVs) represent an important mode of intercellular communication by serving as vehicles for transfer between cells of membrane and cytosolic proteins, lipids, and RNA. Deficiencies in our knowledge of the molecular mechanisms for EV formation and lack of methods to interfere with the packaging of cargo or with vesicle release, however, still hamper identification of their physiological relevance in vivo. In this review, we focus on the characterization of EVs and on currently proposed mechanisms for their formation, targeting, and function.